Control by the brain of visual processing in the retina is the main focus of the project. A circadian clock in the Limulus brain generates efferent optic nerve activity that modulates retinal structure and function of the lateral eye. This discovery opens up new areas of research. It provides the first evidence for the direct efferent control of photoreceptor function and metabolism. Specific aims are to investigate: 1. efferent control of retinal function 2. efferent neurotransmitter(s) 3. cellular mechanisms of efferent action 4. circadian modulation of photoreceptor metabolism 5. circadian organization of the visual system 6. role of retinal circadian rhythms in behavior A major effort will be made to identify the efferent neurotransmitter(s) and determine their mechanisms of action on retinal function. Octopamine is one. It activates adenylate cyclase in photoreceptors producing a second transmitter, cAMP. A neuropeptide (approximately 2000 daltons) appears to be another, and recent work points to a circulating light-adapting hormone. We will try to understand how these transmitters produce multiple circadian changes in the structure and function of the retina. We will use techniques of anatomy, physiology, neurochemistry, NMR, and behavior. Our physiological techniques provide long-term ERG (less than 5 months), optic nerve (approximately 5 days), and photoreceptor (approximately 50 hours) recordings from the lateral eye in situ. They also provide precise control of the efferent input to the retina. We have developed techniques to record the clock's activity from isolated brains (approximately 2 days) and are working on techniques to record from isolated photoreceptors. No other animal model we know offers all these experimental advantages. They are ideally suited for investigating the efferent control of retinal function and establish Limulus as an appropriate model for this research. The primary tenet of the project is that further comprehensive studies of the Limulus visual system will yield fundamental understandings of basic mechanisms of visual processing. Past studies with Limulus mark a milestone in vision research. The proposed studies may prove equally productive. They should contribute significantly toward our long-term goal understanding the functional organization of the visual system.